Cytomegalovirus infection

Summary

Cytomegalovirus infection (MONDO:0005132) is a disease with 1 cohort gene (8 GWAS associations across 5 studies) and 278 clinical trials. Top therapeutic interventions include valganciclovir, ganciclovir, and letermovir.

At a glance

• Cohort genes: 1
• GWAS associations: 8
• Clinical trials: 278

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cytomegalovirus infection
Mondo ID	MONDO:0005132
EFO	EFO:0001062
MeSH	D003586
NCIT	C53649
SNOMED CT	28944009
UMLS	C0010823
MedGen	8239
Is cancer (heuristic)	no

Also known as: CMV infection · Cytomegaloviral infection · HCMV infection

Data availability: 8 GWAS associations (5 studies).

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › viral infectious disease › primary viral infectious disease › Herpesviridae infectious disease › cytomegalovirus infection

Related subtypes (7): herpetic gastritis, herpes simplex infectious disease, Epstein-Barr virus infection, human herpesvirus 8 infection, varicella zoster infection, roseolovirus infectious disease, congenital herpes virus infection

Subtypes (4): cytomegalovirus retinitis, fetal cytomegalovirus syndrome, idiopathic disseminated cytomegalovirus infection, cytomegalovirus pneumonia

Genetics & variants

GWAS landscape

8 GWAS associations across 5 studies. Top hits map to 7 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs145791081	4e-08	RBFOX1	?	3.31
rs117683430	2e-07	ISCA1P3 - ARL2BPP8	?	2.39
rs1555594574	3e-07	LINC00511	?
rs79661622	4e-07	HPCAL1	?	0.27
rs7902091	7e-07	CTNNA3	A	5.33
rs140964551	7e-07	NID1	?
rs77488831	8e-07	LSAMP	?	0.14
rs28688712	1e-06	EXD3	?	0.59

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST001833	Borglum AD	2013	888	0	Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.
GCST90473067	UK Biobank Whole-Genome Sequencing Consortium	2025	261	458,179	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90448196	Shapira G	2023	0	0	Genomic Markers Associated with Cytomegalovirus DNAemia in Kidney Transplant Recipients.
GCST90085704	Casto A	2021	0	0	Genetic Variants Associated with Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation.
GCST90092529	Casto A	2021	0	0	Genetic Variants Associated with Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	7

MAF distribution

Bucket	Variants
common (>=0.05)	8
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	7
5_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs145791081	16	5715120	C>G	0.05	intron_variant	RBFOX1	4e-08	Tier 4: intronic/intergenic
rs117683430	17	54656317	G>A	0.05	intron_variant	ISCA1P3 - ARL2BPP8	2e-07	Tier 4: intronic/intergenic
rs1555594574	17	72304712	TGA>T,TGAGA	0.05	intron_variant	LINC00511	3e-07	Tier 4: intronic/intergenic
rs79661622	2	10419186	T>TG	0.05	5_prime_UTR_variant	HPCAL1	4e-07	Tier 2: splice/UTR
rs7902091	10	66838534	C>A,T	0.05	intron_variant	CTNNA3	7e-07	Tier 4: intronic/intergenic
rs140964551	1	236003668	G>A	0.05	intron_variant	NID1	7e-07	Tier 4: intronic/intergenic
rs77488831	3	116387566	G>A	0.05	intron_variant	LSAMP	8e-07	Tier 4: intronic/intergenic
rs28688712	9	137352913	C>A,T	0.05	intron_variant	EXD3	1e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTNNA3	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
CTNNA3	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
CTNNA3	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTNNA3	HGNC:2511	ENSG00000183230	Q9UI47	Catenin alpha-3	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTNNA3	Catenin alpha-3	May be involved in formation of stretch-resistant cell-cell adhesion complexes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTNNA3	Other/Unknown	no		Alpha_catenin, Vinculin/catenin, Alpha-catenin/vinculin-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	1
heart right ventricle	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTNNA3	211	broad	marker	corpus callosum, heart right ventricle, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNA3	2,306

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CTNNA3	Q9UI47	81.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1	2407.4×	0.002	CTNNA3
regulation of ventricular cardiac muscle cell action potential	1	1404.3×	0.002	CTNNA3
regulation of heart rate by cardiac conduction	1	374.5×	0.004	CTNNA3
cell-cell adhesion	1	101.5×	0.012	CTNNA3
cell migration	1	61.5×	0.016	CTNNA3

Therapeutics

Drugs indicated for this disease

2 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Letermovir	Approved (phase 4)
Maribavir	Approved (phase 4)
Acyclovir	Phase 3 (in late-stage trials)
Adefovir Dipivoxil	Phase 3 (in late-stage trials)
Artesunate	Phase 3 (in late-stage trials)
Brincidofovir	Phase 3 (in late-stage trials)
Everolimus	Phase 3 (in late-stage trials)
Foscarnet	Phase 3 (in late-stage trials)
Ganciclovir	Phase 3 (in late-stage trials)
Levocarnitine	Phase 3 (in late-stage trials)
Mycophenolic Acid	Phase 3 (in late-stage trials)
Phenol	Phase 3 (in late-stage trials)
Valganciclovir	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Valacyclovir.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTNNA3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CTNNA3

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CTNNA3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 278.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	108
PHASE2	42
PHASE1	42
PHASE3	32
PHASE4	30
PHASE1/PHASE2	15
PHASE2/PHASE3	7
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT07009548	PHASE4	ENROLLING_BY_INVITATION	CytoGam for CMV Infection or Disease in Solid Organ Transplant Recipients
NCT07430683	PHASE4	ACTIVE_NOT_RECRUITING	Valganciclovir Prophylaxis Versus Preemptive Therapy for Cytomegalovirus in Living Donor Kidney Transplant Recipients
NCT07450365	PHASE4	NOT_YET_RECRUITING	Evaluation of Long-term Efficacy of 4 to 6-month Course Antiviral Therapy for Neurodevelopmental Impairments Caused by Congenital Cytomegalovirus Infection
NCT07569653	PHASE4	RECRUITING	Letermovir Prophylaxis Duration Guided by CMV-Specific T-cell Monitoring After Allo-HSCT.
NCT07570433	PHASE4	NOT_YET_RECRUITING	HORUS-Cytomegalovirus Open Proof-of-concept Exploratory Trial
NCT07571135	PHASE4	NOT_YET_RECRUITING	Letermovir vs Valganciclovir in CMV R+ Kidney Transplant
NCT00002146	PHASE4	COMPLETED	Safety and Efficacy of Intravenous Magnesium Sulfate in Modulating Changes in Symptoms and Divalent Cation Levels Associated With Foscavir Therapy: A Phase IV Randomized, Double-Blind, Placebo-Controlled, Cross-Over, Pilot Study
NCT00264290	PHASE4	COMPLETED	Valganciclovir to Reduce T Cell Activation in HIV Infection
NCT00264368	PHASE4	TERMINATED	Ganciclovir Pharmacokinetics in Patients Undergoing Continuous Renal Replacement Therapy
NCT00373165	PHASE4	COMPLETED	Prophylaxis With Ganciclovir Improves Graft Survival in Renal Allograft Recipients
NCT00431353	PHASE4	COMPLETED	VICTOR Study - A Study of Valcyte (Valganciclovir po) Compared to Ganciclovir iv in Patients With Cytomegalovirus (CMV) Disease Who Are Solid Organ Transplant Recipients
NCT00730769	PHASE4	COMPLETED	Valganciclovir for Treatment of Cytomegalovirus Infection in Solid Organ Transplant Patients
NCT01037712	PHASE4	TERMINATED	In UTERO Treatment of Cytomegalovirus Congenital Infection With Valacyclovir
NCT01354301	PHASE4	COMPLETED	Efficacy and Safety of Induction Strategies Combined With Low Tacrolimus Exposure in Kidney Transplant Recipients Receiving Everolimus or Sodium Mycophenolate
NCT01552369	PHASE4	COMPLETED	CMV Antiviral Prevention Strategies in D+R-Liver Transplants (CAPSIL)
NCT01663740	PHASE4	COMPLETED	A Study on Spermatogenesis in Male Renal Transplant Recipients Receiving Valganciclovir (Valcyte®) Versus Untreated Matched Controls
NCT01927588	PHASE4	UNKNOWN	Evaluation of Early Use of Everolimus (EVE) on Cytomegalovirus (CMV) Infection in Renal Transplant Recipients
NCT02084446	PHASE4	COMPLETED	Everolimus + Very Low Tacrolimus vs Enteric-coated Mycophenolate Sodium + Low Tacrolimus in de Novo Renal Transplant
NCT02134184	PHASE4	COMPLETED	The Influence of Chronic CMV Infection on Influenza Vaccine Responses
NCT02328963	PHASE4	COMPLETED	Proportion of CMV Seropositive Kidney Transplant Recipients Who Will Develop a CMV Infection When Treated With an Immunosuppressive Regimen Including Everolimus and Reduced Dose of Cyclosporine Versus an Immunosuppressive Regimen With Mycophenolic Acid and Standard Dose of Cyclosporine A
NCT02550639	PHASE4	COMPLETED	Prospective, Randomized Study for Predicting Human Cytomegalovirus (hCMV) Infection Based on Baseline hCMV Specific T-cell Response in Kidney Transplant
NCT02671318	PHASE4	UNKNOWN	Conversion to Sirolimus: Effects in Cytomegalovirus Infection Recurrence
NCT02683291	PHASE4	COMPLETED	Sirolimus Associated With Tacrolimus at Low Doses in Elderly Kidney Transplant Patients
NCT02943057	PHASE4	COMPLETED	Topical 2% Ganciclovir Eye Drop for CMV Anterior Uveitis / Endotheliitis
NCT03004261	PHASE4	COMPLETED	CMV-CTL for the Treatment of CMV Infection After HSCT
NCT04183738	PHASE4	WITHDRAWN	Inflammation and Co-Infections in D²EFT
NCT04278547	PHASE4	UNKNOWN	Multicenter Clinical Trial to Evaluate the Efficacy of a Preventive Strategy Against CMV Infection in Heart Transplant Patients, Based on the Specific T Cells Response
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT04936971	PHASE4	WITHDRAWN	Introduction of mTor Inhibitors and the Activation of the Cytomegalovirus (CMV) -Specific Cellular Immune Response
NCT04832607	PHASE3	RECRUITING	Multivirus-specific T-cell Transfer Post SCT vs AdV, CMV and EBV Infections
NCT06334497	PHASE3	RECRUITING	Letermovir-based Dual Therapy for Treatment of Cytomegalovirus Infections
NCT06407232	PHASE3	RECRUITING	Letermovir (Prevymis) for CMV in Kidney and Pancreas Transplant Recipients
NCT07225972	PHASE3	NOT_YET_RECRUITING	Phase 3 Randomized Trial for Refractory ADV or CMV Infection With Family Matched CTLs and Standard of Care (SOC) vs SOC Alone
NCT00000584	PHASE3	COMPLETED	Transfusion-Transmitted Cytomegalovirus Prevention in Neonates
NCT00001038	PHASE3	COMPLETED	A Study of Valacyclovir Hydrochloride in the Prevention of Life-Threatening Cytomegalovirus Disease in HIV-Infected Patients
NCT00001082	PHASE3	COMPLETED	The Safety and Effectiveness of Adefovir Dipivoxil in the Treatment of HIV-Infected Patients
NCT00001100	PHASE3	COMPLETED	A Phase III Study to Evaluate the Safety and Efficacy of Ganciclovir (Dihydroxypropoxymethyl Guanine [DHPG]) Treatment of Symptomatic Central Nervous System (CNS) Congenital Cytomegalovirus (CMV) Infections.
NCT00004278	PHASE3	COMPLETED	Phase III Randomized, Controlled Study of Ganciclovir for Symptomatic Congenital Cytomegalovirus Infection
NCT00006145	PHASE3	COMPLETED	Preventing Cytomegalovirus (CMV) Organ Damage With Valganciclovir in People With HIV

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VALGANCICLOVIR	4	30
GANCICLOVIR	4	27
LETERMOVIR	4	17
FOSCARNET	4	10
MYCOPHENOLIC ACID	4	10
VALACYCLOVIR	4	6
EVEROLIMUS	4	4
MARIBAVIR	4	4
DARUNAVIR	4	3
ARTESUNATE	4	2
CIDOFOVIR ANHYDROUS	4	2
MYCOPHENOLATE MOFETIL	4	2
PREDNISONE	4	2
TACROLIMUS ANHYDROUS	4	2
ACYCLOVIR	4	1
ADEFOVIR DIPIVOXIL	4	1
BASILIXIMAB	4	1
BRINCIDOFOVIR	4	1
DOLUTEGRAVIR	4	1
LEVOCARNITINE	4	1
MAGNESIUM SULFATE	4	1
PROBENECID	4	1
RITONAVIR	4	1
SIROLIMUS	4	1
POSOLEUCEL	3	2
CARNITINE	3	1
ESTROGEN	3	1
FIACITABINE	2	1
LOBUCAVIR	2	1
MCMV-3068A	2	1